ABSTRACT
Objective
Depression is often a serious and debilitating illness in adolescents. Unfortunately, a significant number of adolescents do not respond to antidepressant medications or psychotherapy. Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment
intervention shown to benefit depression in adults. This study considered rTMS as an adjunctive treatment in adolescents with major depressive disorder.

Method
This prospective, open, multicenter trial of active adjunctive rTMS was conducted with eight adolescents with DSM-IV-TR major depressive disorder (MDD) who had not responded sufficiently to two adequate antidepressant medication trials.

All subjects were maintained on a stable dose of a selective serotonin reuptake inhibitor during the trial. Thirty daily rTMS treatments were given five days per week over six to eight weeks. rTMS was applied to the left dorsolateral prefrontal cortex (120 percent of motor threshold; 10 Hz; four-second trains; 26-second intertrain interval; 75 trains) for a total of 3,000 stimulations per treatment session.

Results
Seven of eight adolescents completed all 30 treatments. rTMS was well tolerated, and no significant safety issues were identified. Suicidal ideation was present at baseline in 3 of the adolescents, and it improved during treatment.

The primary outcome measure was the Children’s Depression Rating Scale-Revised (CDRS-R); results improved significantly from baseline (mean [SD]) (65.9 [6.6]) to treatment 10 (50.9 [12]), P < .02.

The CDRS-R scores continued to improve through the rTMS treatment series at treatment 20 (40.1 [14]), P < .01; treatment 30 (32.6 [7.3]), P < .0001; and at six-month follow-up (32.7 [3.8]), P < .0001.

Conclusions
This prospective open trial suggests that rTMS is a safe, feasible, and potentially effective adjunctive therapy for treatment-resistant MDD in adolescents.

Read “Repetitive rTMS Provides a Safe, Effective Alternative for Some Adolescents with Major Depressive Disorder” in PsychUpdate, Vol. 3, No. 2, 2011.

A related trial is currently recruiting participants:
Investigation of repetitive transcranial magnetic stimulation in depressed adolescents

This research proposal aims to better understand the neurobiology of depression in adolescents and how repetitive transcranial magnetic stimulation (rTMS) may therapeutically impact brain function and mood.

This research is first study evaluating metabolic changes in the brain as a result of rTMS treatment in depressed adolescents using magnetic resonance spectroscopy (MRS). The approach will also optimize individualized rTMS treatment by using an efficient and theoretically more accurate coil placement technique known as Beam F3 positioning.

The investigators primary hypothesis is that adolescents treated with rTMS will have significant mood improvement and show no evidence of cognitive decline or worsening suicidality. The study will lead to a better understanding of the mechanism of rTMS in the treatment of depression and will allow clinicians to have greater ability to individualize depression treatment; this could potentially decrease the number of ineffective treatments and/or risk for serious side effects.

Read more at Clinical Trials.gov, NCT01502033.

Findings indicate that bevacizumab (Avastin), a drug commonly used off label to treat new blood vessel growth due to wet AMD, is as effective as ranibizumab (Lucen­tis) for the treatment of AMD when given at the same dosing schedule.

An article about the study was published in the May 19, 2011 issue of The New England Journal of Medicine.  

Read “Bevacizumab Expands Treatment Options for Patients With Age-Related Macular Degeneration” in Ophthalmology Update. 

ABSTRACT
Background
Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data.

Methods
A multicenter, single-blind, noninferiority trial randomly assigned 1,208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at one year, with a noninferiority limit of five letters on the eye chart.

 Results
Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively.

Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively.

Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive.

The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance).

Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20).

The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1 percent vs. 19.0 percent; risk ratio, 1.29; 95 percent confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.

Conclusions
At one year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study.

An article about the study was published in the Dec. 8, 2011 issue of The New England Journal of Medicine.

ABSTRACT
Background
Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease.

Methods
We evaluated the prevalence and character of demyelinating cortical lesions in patients with multiple sclerosis. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions.

In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. Patients with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination. Using immunohistochemistry, we characterized cortical lesions with respect to: 

• Demyelinating activity
• Inflammatory infiltrates
• The presence of meningeal inflammation
• A topographic association between cortical demyelination and meningeal inflammation.

Diagnoses were ascertained in a subgroup of 77 patients (56%) at the last follow-up visit (at a median of 3.5 years). 

Results
Cortical demyelination was present in 53 patients (38%) (104 lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks). 

Twenty-five patients with cortical demyelination had definite multiple sclerosis (81% of 31 patients who underwent long-term follow-up), as did 33 patients without cortical demyelination (72% of 46 patients who underwent long-term follow-up).

In representative tissues, 58 of 71 lesions (82%) showed CD3+ T-cell infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated demyelination.

Meningeal inflammation was topographically associated with cortical demyelination in patients who had sufficient meningeal tissue for study.

Conclusions
In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation. 

(Funded by the National Multiple Sclerosis Society and the National Institutes of Health.)

A description of the study, which is currently in the phase of active recruitment, is published in the September 2011 issue of Fertility and Sterility.

ABSTRACT
Objective
To present the rationale, design, and methodology of the Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT) study

Design
Randomized clinical trial

Setting
Two academic medical centers

Patients
Premenopausal women with symptomatic uterine fibroids

Interventions
Participants are randomized to two U.S. Food and Drug Administration–approved minimally invasive treatments for uterine leiomyomas: uterine artery embolization and magnetic resonance–guided focused ultrasound.

Main Outcome Measures
The primary endpoint is defined as the need for an additional intervention for fibroid symptoms following treatment. Secondary outcomes consist of:

• Group differences in symptom alleviation
• Recovery trajectory
• Health-related quality of life
• Impairment of ovarian reserve
• Treatment complications
• Economic impact of these issues

Results
The trial is currently in the phase of active recruitment.

Conclusions
This randomized clinical trial will provide important evidence-based information for patients and health care providers regarding optimal minimally invasive treatment approach for women with symptomatic uterine leiomyomas.

Authors
Esther V.A. Bouwsma, M.D., Gina K. Hesley, M.D., David A. Woodrum, M.D., Ph.D., Amy L. Weaver, M.S., Phyllis C. Leppert, M.D., Ph.D., Lisa G. Peterson, R.N., M.A.N., Elizabeth A. Stewart, M.D.

Clinical Trial registration
NCT00995878

ABSTRACT
Suicide is a public health problem and a leading cause of death. The number of people thinking seriously about suicide, making plans, and attempting suicide is surprisingly high. In total, primary care clinicians write more prescriptions for antidepressants than mental health clinicians and see patients more often in the month before their death by suicide.

Treatment of depression by primary care physicians is improving, but opportunities remain in addressing suicide-related treatment variables. Collaborative care models for treating depression have the potential both to improve depression outcomes and decrease suicide risk. Alcohol use disorders and anxiety symptoms are important comorbid conditions to identify and treat.

Management of suicide risk includes understanding the difference between risk factors and warning signs, developing a suicide risk assessment, and practically managing suicidal crises.

Authors
Anna K. McDowell, M.D., Timothy W. Lineberry, M.D., and J. Michael Bostwick, M.D.

Joseph A. Dearani, M.D., of the Department of Cardiovascular Surgery at Mayo Clinic discusses results of a study of patients 40 years or older treated for tetralogy of Fallot, one of the most common cyanotic congenital heart lesions.  The paper was published in the December 1, 2010 issue of Mayo Clinic Proceedings.

ABSTRACT
Objective
To report the outcomes of patients with tetralogy of Fallot (TOF) undergoing surgical repair at age 40 years or older.

Patients and Methods
We reviewed records of patients (age, ≥40 years) who underwent TOF repair from January 1, 1970, through December 31, 2007. Symptoms, palliative procedures, surgical reports, and long-term outcomes were analyzed.

Results
Fifty-two patients (30 men [58%]) had surgery at a mean ± SD age of 50±8 years; 27 (52%) had prior palliative surgery at a mean ± SD age of 17±11 years. Procedures for TOF repair included pulmonary valve replacement (n=10), transannular patch (n=10), and native pulmonary valve preservation (n=32). The 30-day mortality rate was 6% (stroke, n=2; ventricular fibrillation, n=1). A mean ± SD follow-up of 14.9±9.3 years was feasible in 48 of 49 survivors; improvement in functional class was observed in 42 patients. Reoperation was performed in 7 patients (4 for pulmonary regurgitation). Twenty-nine patients died (mean ± SD age, 65±12 years); causes of death were cardiac (n=7), noncardiac (n=4), and unknown (n=18). Mean ± SD age at death was younger in patients with previous palliation (59±11 years vs 70±12 years; P=.03). The 10-year survival rate was lower than expected compared with an age- and sex-matched population (73% vs 91%; P<.001).

Conclusion
Complete repair of TOF in patients 40 years or older is feasible but carries increased operative risk. Surgical survivors have improvement in functional class; however, survival remains lower than expected. Reduced survival and need for reoperation emphasize the importance of pulmonary valve replacement at the time of initial repair and long-term follow-up.

Christine H. Attenhofer Jost, M.D., Heidi M. Connolly, M.D.,  Harold M. Burkhart, M.D., Christopher G. Scott, M.S., Joseph A. Dearani, M.D., Aisling J. Carroll, M.D., A. J. Tajik, M.D. 

ABSTRACT
Background
Fully covered self-expandable metal stents (FCSEMSs) have been proposed for the treatment of benign esophageal diseases.

Objective
To review our experience with FCSEMSs in patients with benign esophageal diseases.

Design
Retrospective case review of patients who underwent FCSEMS placement for benign esophageal diseases, including:

1. Benign strictures from GERD—caustic and idiopathic causes
2. Radiation-induced strictures
3. Anastomotic strictures
4. Esophageal fistulae/leaks
5. Esophageal perforations

Setting
Tertiary-care medical center. 

Patients
This study involved 37 male and 19 female patients (average age 60 years, range 25-94 years) who underwent FCSEMS placement. 

Intervention
FCSEMS placement.

Main outcome measurements
Technical success with stent placement and removal, stent migration, long-term and short-term complications, and treatment success according to clinical symptoms, follow-up endoscopy, or imaging.

Results
Stent placement was successful in 100 of 107 (93%) procedures, with a total of 104 stents placed. Migration was noted in 37 of 104 (35.6%) stents and was seen more frequently with proximal stents and stents placed for anastomotic strictures. Initial treatment success was seen in 56% of patients with any stricture and in 38% of patients with a fistula/leak or perforation, although data to document long-term resolution were lacking. 

Limitations
This was a retrospective review with patients selected from a tertiary-care medical center. Two endoscopists performed the majority of procedures. 

Conclusion
Temporary placement of FCSEMSs for benign esophageal diseases has moderate clinical efficacy and is limited by stent migration. Removability was easily demonstrated. Newer developments in stent design may improve clinical outcomes for these patients.

J. C. Bakken, M.D., Louis M. Wong Kee Song, M.D.,  Piet C. de Groen, M.D., Todd H. Baron, M.D.

The Alzheimer’s Association and the National Institute on Aging of the National Institutes of Health recently published updated guidelines defining Alzheimer’s disease and MCI. The guidelines identify two new phases of the disease: presymptomatic and mildly symptomatic but predementia. Dr. Petersen discusses the significance of the new stage of predementia.

Large, giant and wide-necked aneurysms are traditionally challenging to treat effectively. In this flow diversion technique, a device is placed across the aneurysm neck to divert blood flow back to the normal vessel and eventually lead to occlusion of the aneurysm.

Dr. Lanzino and Mayo Clinic were involved in early clinical studies leading to U.S. Food and Drug Administration (FDA) approval of this device.